Positron Emission Tomography of CD47/SIRPα Axis and Image-Informed Therapeutic Design

CD47/SIRPα immune axis is of substantial clinical interest for innate cancer immunotherapy. Development on this axis has largely focused on monoclonal antibody agents and combination therapy strategies. Clinical use is challenging due to dose limiting side effects and severe anemia. Better understanding of the whole-body dynamics of CD47/SIRPα can be used to improve the developmental and therapeutic strategies targeting this axis. Herein, we developed anti-CD47 and anti-SIRPα radiotracers with good yields and stability. CD47/SIRPα biodistribution showed consistent whole-body results in healthy and colorectal cancer (CT26) allograft mice, demonstrating significant uptake in normal organs liver and spleen in addition to tumor accumulation of these agents. Enhancing immunogenicity via low-dose radiotherapy had no impact on over-all biodistribution but caused small, significant changes for anti-SIRPα tumor uptake. Antibody PEGylation of the anti-SIRPα tracer was further able to modify the whole-body distribution and reduce splenic uptake. These findings suggest that SIRPα targeted agents may benefit from co-therapies and drug delivery systems to optimize tumor uptake. Our work highlights the importance of in vivo molecular imaging in addition to in vitro and ex vivo assays when evaluating therapeutic designs.